The game follows Zeke and Julie as they battle monsters with an assortment of peculiar weapons. They must fight through over fifty top-down levels and rescue helpless people in each world. By saving the people from the monsters, the player can advance to the next level.

Zombies Ate My Neighbors received some censorship upon different releases due to its horror elements. It became a cult classic years after its release and a sequel entitled Ghoul Patrol was released in 1994 by LucasArts. However, it was not as well received as its predecessor and no further sequels were produced. It has since then become a cult classic among video games.